Current Issue

Exogenous administration of zinc chloride improves lung ischemia/reperfusion injury in rats

WANG Shu-Yuan¹, XU Jun-Peng², CHENG Yuan², HUANG Man², CHEN Si-An², LI Zhuo-Lun², ZHANG Qi-Hao², DAI Yong-Yue², YOU Li-Yi³, WANG Wan-Tie^2,*

¹Department of Respiratory Medicine, Wenzhou People's Hospital, Wenzhou 325400, China；²Institute of Ischemia/Reperfusion Injury, Wenzhou Medical University, Wenzhou 325035, China；³Department of Ultrasound, Wenzhou People's Hospital, Wenzhou 325400, China

Abstract

The aim of this study was to investigate the contribution of lung zinc ions to pathogenesis of lung ischemia/reperfusion (I/ R) injury in rats. Male Sprague Dawley (SD) rats were randomly divided into control group, lung I/R group (I/R group), lung I/R + low-dose zinc chloride group (LZnCl2+I/R group), lung I/R + high-dose ZnCl2 group (HZnCl2+I/R group), lung I/R + medium-dose ZnCl2 group (MZnCl2+I/R group) and TPEN+MZnCl2+I/R group (n = 8 in each group). Inductively coupled plasma mass spectrometry (ICP-MS) was used to measure the concentration of zinc ions in lung tissue. The degree of lung tissue injury was analyzed by observing HE staining, alveolar damage index, lung wet/dry weight ratio and lung tissue gross changes. TUNEL staining was used to detect cellular apoptosis in lung tissue. Western blot and RT-qPCR were used to determine the protein expression levels of caspase-3 and ZIP8, as well as the mRNA expression levels of zinc transporters (ZIP, ZNT) in lung tissue. The mitochondrial membrane potential (MMP) of lung tissue was detected by JC-1 MMP detection kit. The results showed that, compared with the control group, the lung tissue damage, lung wet/dry weight ratio and alveolar damage index were significantly increased in the I/R group. And in the lung tissue, the concentration of Zn2+ was markedly decreased, while the cleaved caspase-3/caspase-3 ratio and apoptotic levels were significantly increased. The expression levels of ZIP8 mRNA and protein were down-regulated significantly, while the mRNA expression of other zinc transporters remained unchanged. There was also a significant decrease in MMP. Compared with the I/R group, both MZnCl2+I/R group and HZnCl2+I/R group exhibited significantly reduced lung tissue injury, lung wet/dry weight ratio and alveolar damage index, increased Zn2+ concentration, decreased ratio of cleaved caspase-3/caspase-3 and apoptosis, and up-regulated expression levels of ZIP8 mRNA and protein. In addition, the MMP was significantly increased in the lung tissue. Zn2+ chelating agent TPEN reversed the above-mentioned protective effects of medium-dose ZnCl2 on the lung tissue in the I/R group. The aforementioned results suggest that exogenous administration of ZnCl2 can improve lung I/R injury in rats.

Key words: zinc ion; lung ischemia/reperfusion injury; apoptosis; mitochondrial membrane potential

Received: 　　Accepted:

Corresponding author: 王万铁　　E-mail:

DOI: 10.13294/j.aps.2025.0038

Citing This Article：

WANG Shu-Yuan, XU Jun-Peng, CHENG Yuan, HUANG Man, CHEN Si-An, LI Zhuo-Lun, ZHANG Qi-Hao, DAI Yong-Yue, YOU Li-Yi, WANG Wan-Tie. Exogenous administration of zinc chloride improves lung ischemia/reperfusion injury in rats. Acta Physiol Sin 2025; 77 (5): 811-819 (in Chinese with English abstract).